Background: Disability resulting from stroke and traumatic brain injury represent the main cause of long term disability among adults. There are no universally accepted treatments available for the treatment of this condition and the financial, personal, familiar and social cost of this disability cannot be underestimated. Preliminary data from different laboratories has shown that it is possible to modulate plastic processes in the lesioned brain by pharmacological, brain stimulation and somatosensory stimulation techniques. The purpose of this Z01 is to characterize the most promising techniques to improve cortical plasticity in these patients in order to enhance functional recovery. Findings this year: From a pathophysiological point of view, we found in cerebellar stroke patients that short intracortical inhibition (SICI) was decreased in M1contralesional compared to M1ipsilesional in the patient group in the absence of side-to-side differences in controls. There were no significant inter-hemispheric or between-group differences in resting motor thresholds, intracortical facilitation, or corticomotor excitability. These results document disinhibition of M1contralesional in the chronic phase after cerebellar stroke. In patients with subcortical strokes (not involving the cerebellum), we found an abnormal persistence of SICI in the ipsilesional M1 during movement preparation that was absent in age-matched controls. Additionally, resting SICI was reduced in the patient group relative to controls. These findings document deficient premovement modulation of intracortical inhibition in the ipsilesional M1 of patients with chronic stroke, an abnormality that might contribute to deficits in motor control of the paretic hand, presenting a possible target for correction in the framework of developing novel therapeutic interventions after chronic stroke. We have also implemented interventional trials in stroke patients. We participated in the first randomized parallel controlled trial assessing the feasibility, safety, and efficacy of virtual reality using Wii gaming technology in stroke rehabilitation and the results may serve as the basis for a larger multicentre trial. We determined that application of multiple sessions of somatosensory stimulation to the paretic limb could facilitate training effects on motor function after subacute stroke depending on the intensity of stimulation. It was proposed that careful dose-response studies are needed to optimize parameters of somatosensory stimulation before designing costly, larger double-blind multicenter clinical trials. We carried out an extensive multicentric review of the present status of the implementation of brain computer interfaces in neurorehabilitation. Additionally, we were able to determine that combination of interventions including transcranial direct current stimulation applied to the ipsilesional motor cortex and somatosensory stimulation applied to the paretic hand resulted in a substantial improvement in the number of correct key presses performed with the paretic hand relative to control interventions. These performance differences were maintained 1 and 6 days after the end of the training. The results indicate that combining peripheral nerve and cortical stimulation can facilitate the beneficial effects of training on motor performance beyond levels reached with each intervention alone, a finding of relevance for the neurorehabilitation of motor impairments after stroke. All together we advanced our understanding of the mechanisms underlying motor stroke disability and in the development of interventions that could facilitate functional recovery after chronic stroke.